Journal article

Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium

Annegien Broeks, Marjanka K Schmidt, Mark E Sherman, Fergus J Couch, John L Hopper, Gillian S Dite, Carmel Apicella, Letitia D Smith, Fleur Hammet, Melissa C Southey, Laura J Van 't Veer, Renate de Groot, Vincent THBM Smit, Peter A Fasching, Matthias W Beckmann, Sebastian Jud, Arif B Ekici, Arndt Hartmann, Alexander Hein, Ruediger Schulz-Wendtland Show all

Human Molecular Genetics | OXFORD UNIV PRESS | Published : 2011

Abstract

Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations with ER+ than ER- tumors for six of the eight loci identified in GWAS: rs2981582 (10q26) (P-hetero..

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Awarded by European Community


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Awarded by European Union


Awarded by National Health and Medical Research Council of Australia


Awarded by National Cancer Institute, National Institutes of Health


Awarded by Dutch Cancer Society


Awarded by Fondo de Investigacion Sanitario


Awarded by Federal Ministry of Education and Research (BMBF) Germany


Awarded by Deutsche Krebshilfe e.V


Awarded by Academy of Finland


Awarded by National Health and Medical Research Council (NHMRC)


Awarded by US Army Medical Research and Material Command


Awarded by Stichting tegen Kanker


Awarded by German Federal Ministry of Education and Research


Awarded by National Institutes of Health


Awarded by NCI Specialized Program of Research Excellence (SPORE) in breast cancer


Awarded by Norwegian Research council


Awarded by Cancer Care Ontario


Awarded by Northern California Cancer Center


Awarded by University of Melbourne


Awarded by Cancer Research UK


Awarded by Lon V Smith Foundation



Awarded by The Francis Crick Institute


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

This work was supported by funding from the European Community's Seventh Framework Programme under grant agreement no. 223175 (HEALTH-F2-2009-223175). The BCAC is funded by CR-UK (C1287/A10118, C1287/A7497, C1287/A12014). Meetings of the BCAC have been funded by the European Union COST program (BM0606). D.F.E. is a Principal Research Fellow of CR-UK. The ABCFS study was supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the National Cancer Institute, National Institutes of Health under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry (CFR) and P.I.s. The ABCS study was supported by the Dutch Cancer Society (grants NKI 2001-2423; 2007-3839) and the Dutch National Genomics Initiative. The BBCC study was partly funded by a Grand of ELAN Funding of the University of Erlangen. P.A.F. is partly funded by Dr Mildred Scheel Stiftung of the Deutsche Krebshilfe e.V. The BSUCH study was supported by the Dietmar-Hopp Foundation and the Helmholtz Society. The CGPS study was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council and Copenhagen University Hospital, Herlev Hospital. The CNIO-BCS study was supported by the Red Tematica de Investigacion Cooperativa en Cancer and grants from the Asociacion Espanola Contra Cancer and the Fondo de Investigacion Sanitario (PI081120 to JB and PI081583 to RLM). The GENICA study was supported by the German Human Genome Project and funded by the Federal Ministry of Education and Research (BMBF) Germany (grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114). The Robert Bosch Foundation of Medical Research, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GESBC study was supported by the Deutsche Krebshilfe e.V. (70492) and GESBC genotyping in part by the state of Baden-Wurttemberg through the Medical Faculty of the University of Ulm (P.685). The HABCS study was supported by an intramural grant from Hannover Medical School. The HEBCS study has been financially supported by the Helsinki University Central Hospital Research Fund, Academy of Finland (110663), the Finnish Cancer Society and the Sigrid Juselius Foundation. The KARBAC study was supported by The Swedish Cancer Society, The Gustav V Jubilee Foundation And The Bert von Kantzow Foundation. The KBCP was supported by the Kuopio University Central EVO Research Fund, Academy of Finland, the Finnish Cancer Society, the University of Kuopio and EVO research funding of Vaasa Hospital District. The kConFab and its Clinical Follow-Up study were funded by grants from the National Breast Cancer Foundation, the National Health and Medical Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia and the Cancer Foundation of Western Australia, as well as by NHMRC (grants 145684, 288704 and 454508). The AOCS study was supported by the US Army Medical Research and Material Command (DAMD17-01-1-0729), the Cancer Council Tasmania and Cancer Foundation of Western Australia and The National Health and Medical Research Council of Australia (199600). Amanda B.Spurdle is supported by an NHMRC Senior Research Fellowship, and Georgia Chenevx-Trench by an NHMRC Senior Principal Research Fellowship The LMBC stduy was supported by European Union Framework Programme 6 (Project LSHC-CT-2003-503297) and by the 'Stichting tegen Kanker' (232-2008). The MARIE study was supported by the Deutsche Krebshilfe e.V., (grant70-2892-BR I), the Hamburg Cancer Society, the German Cancer Research Center and the German Federal Ministry of Education and Research (01KH0402). The MCBCS was supported by National Institutes of Health (grant R01 CA122340), and an NCI Specialized Program of Research Excellence (SPORE) in breast cancer (P50 CA116201). The MCCS study was supported by Cancer Council Victoria and by NHMRC (grants 209057, 251533, 396414,504711, 504715). The MEC study was supported by National Institutes of Health (grants R01-CA63464, R37-CA54281). The NBCS study was supported by grants from the Norwegian Research council, (155218/V40, 175240/S10) to ALBD, FUGE-NFR (181600/V11) to VNK and a Swizz Bridge Award to ALBD. The OFBCR was supported by the National Cancer Institute, National Institutes of Health under (grant CA-06-503) and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario (U01 CA69467), Northern California Cancer Center (U01 CA69417), and University of Melbourne (U01 CA69638) and by Cancer Care Ontario. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR nor does the mention of trade names, commercial products or organizations imply endorsement by the US Government or the BCFR. The ORIGO study was supported by the Dutch Cancer Society. The PBCS was supported by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The RBCS study was supported by the Dutch Cancer Society (grant DDHK 2004-3124). The SASBAC study was supported by funding from the Agency for Science, Technology and Research of Singapore (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. The SBCS study was funded by the Breast Cancer Campaign (grant 2004Nov 49) and Yorkshire Cancer Research core funding. SEARCH study was supported by Cancer Research UK grants (C490/A1102, C8197/A10123, C490/A10119, C490/A11020, C1287/A10118) and AMD was funded by CR-UK grant (C8197/A10865). The pathology work in Cambridge was supported by the NIHR Cambridge Biomedical Research Centre and by the Cambridge Experimental Cancer Medicine Centre. The SZBCS was supported by Grant (PBZ_KBN_122/P05/2004). The TBCS was funded by The National Cancer Institute Thailand. The TWBCS study was supported by the Institute of Biomedical Sciences, Academia Sinica, National Sciences Counciland Taiwan Biobank. The UCIBCS study was supported by the National Institutes of Health, National Cancer Institute (grants CA-58860) and the Lon V Smith Foundation (grant LVS-39420).